Stretching of soft tissue (connective tissue and muscle) is an important component of manual (e.g. massage) and movement-based (e.g. yoga) CAM therapies that have been found to be efficacious in clinical trials of chronic and recurrent low back pain (LBP). Although evidence from clinical trials is beginning to show that these CAM treatments are effective in chronic low back pain (LBP), the mechanisms by which these treatments are beneficial remain unknown. We hypothesize that 1) connective tissue (CT) fibrosis, accompanied by nervous system sensitization, can be produced experimentally in a porcine model combining microinjury and movement restriction and 2) in this porcine model, both connective tissue and nervous system pathologies are reversible and can be ameliorated by tissue stretch. This project will set the stage for a future mechanistic study of the effect of tissue stretch in humans. We will compare four groups of mini-pigs (48 pigs, 12 pigs per group) randomized to: 1) movement restriction of the low back and pelvis for 8 weeks, 2) PCT microinjury followed by observation for 8 weeks, 3) PCT microinjury followed by movement restriction for 8 weeks and 4) normal controls. All pigs will undergo weekly ultrasound and gait analysis using wireless orientation sensors (Aim 1). We will then compare two groups of pigs (24 pigs, 12 pigs per group) all with PCT microinjury plus movement restriction for a duration determined by the results of Aim1, followed by 4 weeks without movement restriction during which pigs will be randomized to 1) passive stretching of the trunk or 2) sham stretching (Aim 2). For both Aims, primary outcome measures will be PCT thickness (in vivo), PCT shear plane motion (in vivo), dense PCT collagen bundle spacing (ex vivo), areolar PCT Type-1 procollagen content and areolar PCT stiffness (ex vivo). Secondary outcome measures will be intersegmental motion during gait (in vivo), areolar PCT cell-mediated tissue relaxation (ex vivo), markers of areolar PCT neurogenic inflammation (NGF, IL1-2 and TNF-1) and spinal cord Substance P and CGRP fiber density. We propose that PCT fibrosis and nervous system sensitization are key component of the pathophysiological mechanism leading to LBP chronicity that can be reversed by tissue stretch. Future projects will test the reversibility of these pathological abnormalities and their relationship to clinical improvement in clinical trials using ultrasound-based non-invasive measures of connective tissue structure and biomechanics. Our long term goal is to use this improved mechanistic understanding as a basis for the development of rational integrative treatment guidelines for LBP for maximum therapeutic benefit. PUBLIC HEALTH RELEVANCE: Despite the widespread use of manual and movement-based therapies for the treatment of low back pain (LBP), the mechanisms by which these treatments may promote healing in this condition remain largely unknown. This lack of understanding constrains the development of improved treatments and is an obstacle to the integration of these CAM modalities into the mainstream management of LBP. This study aims to establish a basic mechanism common to manual and movement-based therapies that will strengthen the rationale for these treatments.